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The DSB machinery, which induces the programmed DNA double-strand breaks (DSBs) in the leptotene and zygotene stages during meiosis, is suppressed before the onset of the pachytene stage. However, the biological significance and underlying mechanisms remain largely unclear. Here, we report that ZFP541 is indispensable for the suppression of DSB formation after mid-pachytene. The deletion of Zfp541 in mice causes the aberrant recruitment of DSB machinery to chromosome axes and generation of massive DSBs in late pachytene and diplotene spermatocytes, leading to meiotic arrest at the diplotene stage. Integrated analysis of single-cell RNA sequencing (scRNA-seq) and chromatin immunoprecipitation (ChIP) sequencing data indicate that ZFP541 predominantly binds to promoters of pre-pachytene genes, including meiotic DSB formation-related genes (e.g., Prdm9 and Mei1) and their upstream activators (e.g., Meiosin and Rxra), and maintains their repression in pachytene spermatocytes. Our results reveal that ZFP541 functions as a transcriptional regulator in pachytene spermatocytes, orchestrating the transcriptome to ensure meiosis progression. [Display omitted] • ZFP541 deficiency in spermatocytes causes meiotic arrest at the diplotene stage • Zfp541 deletion causes aberrant DSB generation in spermatocytes after mid-pachytene • ZFP541 represses the expression of meiotic DSB formation genes in pachytene • ZFP541 binds promoters of pre-pachytene genes to maintain their repression in pachytene Xu et al. demonstrate that ZFP541 predominantly maintains the repression of pre-pachytene transcriptional programs, including meiotic DSB formation genes, in pachytene spermatocytes and suppresses aberrant DSB formation after mid-pachytene, thus ensuring meiosis progression. [ABSTRACT FROM AUTHOR]

Abstract: 15 nm diameter SiO2 nanoparticles with a grafted block copolymer consisting of a 5–20 nm rubbery polyhexylmethacrylate (PHMA) inner block and a 30 nm outer block of matrix compatible polyglycidylmethacrylate (PGMA) were synthesized to toughen an epoxy. A systematic study of the effect of block copolymer graft density (from 0.07 to 0.7 chains/nm2) and block molecular weight (from 20 to 80 kg/mol) on the tensile behavior, fracture toughness, and fatigue properties was conducted. It was found that the copolymer grafted SiO2 nanoparticles enhanced the ductility (maximum 60% improvement), fracture toughness (maximum 300% improvement) and fatigue crack growth resistance of the epoxy matrix while maintaining the modulus at loadings of less than 2 vol% of silica core. The PHMA block induced plastic void growth and shear banding. At lower graft density and larger molecular weight of the PHMA block, the nanocomposites exhibited simultaneous improvements in fracture toughness and tensile modulus. The PGMA epoxy compatible block also contributed to the improved fracture energy of the nanocomposites. [Copyright &y& Elsevier]

Polyphenols are important active components of tea. Tea polyphenol oxidase (PPO) catalyzes polyphenols oxidation, hence it is vitally important to the quality and function of black tea. The enzyme was believed to be mostly deactivated during the thermal processing. Here we report the macromolecular fraction of a Chinese black tea (Camellia. sinensis var. Lapsang souchong) infusion oxidized pyrocatechol even at the enzyme's deactivation temperature. Utilizing urea-assisted extraction and ion-exchange chromatography, the PPOs and/or co-enzymes were isolated from the tea infusion and the cold water extracts of fresh tea leaves. The isolates were found to exhibit PPO activities after removing urea by dialysis. A 66.0 kDa PPO with specific activity of 1200 U/mg (K m = 6.973 mM and V max = 15.79 U/min) was purified and characterized to be a glycoprotein with isoelectric point of 4.82. The efficiency of four inhibitors against this PPO are cysteine > EDTA > sodium sulfite > ascorbic acid. The PPOs isolated from black tea infusion reserved 40–80% of activities of their aliquots from fresh tea leaves. It reveals the PPOs can survive the thermal processing of the black tea, possibly in form of PPO-polyphenol complex. Exploring the biochemistry and oxidation mechanism of tea infusion, this study may empower the future development of tea and plant-based beverages. • A Chinese black tea infusion was found to exhibit polyphenol oxidase (PPO) activity. • Three PPOs were isolated from both the tea leaves and tea infusion by chromatography. • The tea polyphenol oxidase with Mw 66.0 kDa was purified and characterized. • Heat Process-Surviving PPOs possibly exist in the forms of PPO-polyphenol complex. [ABSTRACT FROM AUTHOR]

Exposure to fine particulate matter (PM 2.5) can result in adverse cardiovascular responses including vascular endothelial dysfunction, whereas exercise training can promote cardiovascular health. However, whether exercise training can mitigate adverse vascular response to PM 2.5 has been less studied. In the present study, we aimed to investigate the preventive effect of exercise training on vascular endothelial dysfunction induced by PM 2.5 instillation. Six-week old male Wistar rats (n = 32) were divided into four groups (8 rats per group) by exercise status (sedentary vs. exercised) and PM 2.5 exposure (instilled vs. non-instilled). Rats received treadmill training with moderate-intensity intervals in week 1 to 6, followed by three repeated PM 2.5 instillation on every other day in week 7. Body weight and blood pressure were measured for each rat regularly during exercise training and before sacrifice. At sacrifice, thoracic aortas were isolated for functional response measurement to agonists. Nitric oxide bioavailability and high-density lipoprotein (HDL) function were also assessed. We observed that exercise training significantly reduced the body weight of rats, while PM 2.5 instillation had little effect. Neither exercise training nor PM 2.5 instillation had significant effects on blood pressure changes. However, exercise training effectively prevented endothelium-dependent vasorelaxation dysfunction and nitric oxide bioavailability reduction from subsequent PM 2.5 instillation. In addition, exercise training promoted HDL function which were characterized as increased HDL cholesterol level, cholesterol efflux capacity, and reduced oxidization index; whereas PM 2.5 instillation showed limited adverse impact on HDL function. Collectively, our results indicated that exercise training could promote HDL function and protect against endothelium dysfunction from PM 2.5 instillation. Unlabelled Image • Exercise training significantly reduced the body weight of rats. • PM 2.5 instillation decreased NO bioavailability. • Exercise training promoted HDL function. • Exercise training prevented endothelium dysfunction induced by PM 2.5 instillation. [ABSTRACT FROM AUTHOR]